Tetrahydrobiopterin and the regulation of hypoxic pulmonary vasoconstriction

B. N. Francis, M. R. Wilkins, L. Zhao

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Tetrahydrobiopterin (BH 4) is an essential cofactor for nitric oxide synthases (NOS). This study investigated the effect of increasing BH 4 levels on hypoxia-induced pulmonary vasoconstriction (HPV). Sprague Dawley rats and hph-1 (BH 4 deficient) mice were given BH 4 before and during HPV in an isolated perfused lung preparation. BH 4 inhibited HPV in a concentration-dependent manner and increased NO metabolites in the perfusate. Bradykinin-induced reductions in HPV were blunted in hph-1 mice and pre-administration of BH 4 restored the response. The effect of BH 4 was attenuated by L-NAME (NOS inhibitor), PTIO (NO scavenger), and catalase (H 2O 2 catalyser) administered prior to HPV but enhanced by MnTMPyP (superoxide dismutase mimetic). The effect of BH 4 on HPV was partially recapitulated by NH 4, a stereoisomer that shares antioxidant properties with BH 4 but is not a NOS cofactor. The bioavailability of BH 4 is an important determinant of the pulmonary vascular response to hypoxia. Its effects are mediated via nitric oxide, hydrogen peroxide and its antioxidant properties, and are attenuated by oxidant stress. Pharmacological administration of BH 4 may have therapeutic potential in pulmonary hypertension. Copyright

Original languageEnglish
Pages (from-to)323-330
Number of pages8
JournalEuropean Respiratory Journal
Issue number2
StatePublished - Aug 2010
Externally publishedYes


  • Animal models
  • Hypoxia
  • Nitric oxide
  • Pulmonary hypertension
  • Pulmonary vasoconstriction
  • Superoxide
  • Tetrahydrobiopterin


Dive into the research topics of 'Tetrahydrobiopterin and the regulation of hypoxic pulmonary vasoconstriction'. Together they form a unique fingerprint.

Cite this